Retatrutide, survodutide, orforglipron. The 3 new GLP-1 agonist-based AOMs showed weight loss of up to 20% and are well worth watching.
Novel MOA. "Participants treated with the highest dose of retatrutide achieved a mean weight reduction of 24.2%; this translates to an average absolute weight reduction of about 58 pounds over 11 months of the study. Given that participants had not yet reached a weight plateau at the time the study ended, it appears that full weight reduction efficacy was not yet attained."
An oral option. "We recognize that obesity is a global epidemic and there is a need for a variety of effective medications and administration routes." Specifically, “there is an unmet need for an oral, incretin-based therapy with efficacy similar to that of injectable GLP-1 receptor agonists.” Given that weight loss had not reached a plateau at the 36-week point, they continued, it's possible that longer treatment duration will result in additional reduction in body weight.
Target: glucagon. “By activating both the glucagon and GLP-1 receptors, survodutide may inhibit both appetite and improve energy expenditure. The findings not only show significant weight loss with increasing doses of survodutide, but we also saw a favorable safety profile, reinforcing the potential clinical benefits.” Among survodutide-treated participants in a phase 2 study, more than half lost more than 50% of baseline bodyweight.
T2D + obesity. “Tirzepatide reduces weight in patients who have both obesity and type 2 diabetes to an extent we haven’t seen before, greater than any other clinical trials and other weight loss medications. With a new drug like tirzepatide, it becomes clear we need a weight-centric approach to treating type 2 diabetes when obesity is also present, two conditions that are interwoven for so many Americans.”
Hi-dose SEMA. “To our knowledge, this was the first trial to assess the body weight-lowering effect of an oral GLP-1 analogue in adults with overweight or obesity, without type 2 diabetes. In this population, oral semaglutide 50 mg induced clinically meaningful reductions in body weight, with accompanying improvements in cardiometabolic risk factors.”